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The present experiments are concerned with the attempt to prevent or ameliorate the occurrence of secondary disease deaths in irradiated mice bearing foreign bone marrow grafts; in addition, certain aspects of graft-to-host tolerance in early radiation chimeras have been investigated. It is concluded that specific graft-to-host tolerance may develop relatively early in radiation chimeras, that it is possible to prevent or eliminate secondary disease in homologous radiation chimeras by suitable preirradiation of the marrow donors, and by injection into the chimeras of specific isoantiserum directed against the marrow donor. (Author).
In studies on lymphoid cell chimerism and homograft tolerance in long-lived homologous radiation chimeras, data were collected on life span, and on leukemia and other lesions. The chimeras were hybrid mice (10 - 12 weeks old) exposed to 880 rad of X radiation and injected with bone marrow cells from C3H donors. Out of 119 mice, 65% were dead by age 32 weeks, with symptoms of second ry disease evident in the great majority. Relatively few deaths occurred between 32 and 75 weeks, and the maximum life span was 105 weeks. Histopathological data were obtained from many of these long-lived chimeras. There was an 80% incidence of glomerulosclerosis of moderate to severe degree, and a 20% incidence of arteriolarsclerosis in t e kidney and spleen. Leukemias were observed in 5 out of 54 homologous chimeras. Also, two leukemias occurred in 13 chimeras (15%) which had been injected with lymphoid cells obtained from other long-lived homologous chimeras. The possibility of a causal relationship between s condary disease and the increased incidence of leukemia is briefly discussed. (Author).
The immunological status of lethally irradiated mice protected against the acute effects of irradiation by the transfusion of rat or allelogenic, parental or isogenic bone marrow was studied using the reaction against skin grafts as the indicator system. The data indicated that the radiation chimeras were immunologically unresponsive animals and were, therefore, able temporarily to accept skin grafts from donors foreign to both the irradiated host and the marrow donor. It was concluded that the ultimate rejection of the skin grafts was the result of the recovery of the host's immune response rather than the result of any contribution of donor marrow cells to the immune system. If the animal survives, a specific tolerance towards the bone marrow donor's skin may develop. A possible alternative hypothesis to explain the persistence of the foreign skin grafts despite deaths from "secondary disease" is discussed.
Radiation chimeras and therapy of radiation injuries are discussed.